Multi Vaccine Development Program. Not For Profit Research Society

Controlled Human Malaria Infection/ (CHMI)

Project Name: Controlled Human Malaria Infection (CHMI)

Study Indication: Plasmodium falciparum Controlled Human Malaria Infection (CHMI)

Study Intervention: The study intervention will be Sporozoites of Chloroquine sensitive, P.falciparum NF54 strain delivered via laboratory reared, female Anopheles stephensi mosquitoes. The infected Anopheles will be generated by membrane feeding of erythrocytes infected with Plasmodium falciparum NF54 gametocytes.

Route of administration: The route of Anopheles bite will be the ventral aspect of forearms of the volunteers.

Clinical Development Phase: Phase I

Objectives: The overall objective of the study is to standardize the CHMI model by demonstrating that healthy adult malaria naïve human volunteers can be infected with P. falciparum (NF54 strain) by the bites of experimentally infected female Anopheles stephensi mosquitoes. Through this study the pre-patent period (time to patent parasitaemia), the growth kinetics of the blood stage of P. falciparum parasite in the human blood (by Real Time PCR), safety of the CHMI model and also the immune response elicited in healthy human volunteers will be evaluated.

Current Status: The partner organization for production of Plasmodium falciparum infected Anopheles stephensi has been identified. Medanta Duke Research Institute will be responsible for recruitment, in-house stay for 2-3 weeks and subsequent follow-up of Healthy volunteers. The study will be initiated after obtaining the necessary ethical and regulatory approvals

Rationale: There are no reliable laboratory (in-vitro) or animal (in-vivo) models which can predict the efficacy of a malaria vaccine candidate before they are taken up for field testing. Hence, in a standard clinical development path, malaria vaccine candidates are tested in Phase II field trials (Phase IIb) once the safety and immunogenicity of the vaccine candidate has been established in Phase I trials. This path of development therefore requires: testing in children of a vaccine with no prior information on efficacy, and is also an expensive proposition since it requires long follow-up of subjects and substantial manpower and infrastructure.

To rationalize candidate vaccine selection, malaria vaccine researchers in USA and Europe have developed a Controlled Human Malaria Infection model (CHMI).CHMI allows proof of concept (Phase IIa) studies in healthy subjects before a vaccine candidate is declared qualified for further testing in exposed individuals. Such testing models have been extremely effective in predicting the success/ failure of pre-erythrocytic malaria vaccine candidates.

It is considered important to establish this model in India as there exists a good pipeline of P. falciparum and P. vivax vaccine candidates which are in advanced stages of pre-clinical development and will subsequently require testing in healthy human adults. Since India contributes majorly to the world malaria burden, it is important that to establish capacity in India to down-select those vaccine candidates for further clinical development which show protection when tested in CHMI.

The purpose of this study is to standardize Controlled Human Malaria Infection (CHMI) model in Indian subjects. At a later date, the standardised model will be utilised to test malaria vaccine candidates.

Key Organizations

Organization Role
Malaria Vaccine Development Program (MVDP), New Delhi, India Sponsor and Overall management of the Project
Medanta Duke Research Institute (MDRI), Medanta-The Medicity Hospital Gurgaon, India Clinical Trial Site
Clinical Laboratory-Medanta-The Medicity Hospital, Gurgaon, India Clinical Laboratory
International Center for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India Immunology assessment